AB0110 TRANSCRIPTOMICS-BASED INVESTIGATION OF THE MECHANISM OF ANKYLOSING SPONDYLITIS WITH UVEITIS
Authors: H. Hai, H. Li, B. Deng
Journal: Annals of the Rheumatic Diseases (2022)

Background Spondyloarthritis is a large group of autoimmune diseases that are associated with HLA-B27. Among them, Ankylosing spondylitis is a typical representative of these diseases. In addition to spine and joint involvement, AS has many extra-articular manifestations, among which uveitis is one of the most common extra-articular manifestations of AS.[1]Untreated or inappropriate treatment can lead to serious consequences such as blindness. However, there are few studies on the mechanisms of AS-related uveitis, and the pathogenesis of AS-related uveitis is not fully understood, so there is no way to prevent it. Objectives We performed a whole-blood gene expression profiling and then analyzed gene expression differences between AS-associated uveitis patients and normal controls by bioinformatics methods. Protein–protein interaction network was constructed to predict the relationship among the products of the differentially expression genes (DEGs). Furthermore, module mining and function annotation were applied to assess the interaction network of DEGs.The aim is to find predictive biomarkers for AS-associated uveitis, to further discuss the pathogenesis of AS-associated uveitis in depth, and to provide a reference for clinical precision treatment. Methods This microarray-based discovery study used samples from three patients with AS,classified according to the New York criteria,four patients with AS-associated uveitis, and three gender- and age-matched controls. Total RNA was extracted from whole blood samples and enriched for mRNA after DNA digestion using DNase, and then constructed cDNA libraries were quality-checked with an Agilent 2100 Bioanalyzer and sequenced using an Illumina HiSeq TM 2500 sequencer.The data were normalized and initially screened for differential genes using the DESeq R package in R 4.1.0 Prediction of relationships between products of differentially expressed genes (DEGs) using String database prediction and construction of protein-protein interaction networks in Cytoscape. GO with KEGG analysis of differential genes using ClueGO and CluePedia. Screening for hub genes associated with AS-associated uveitis using cytoHubba. Results We initially screened 14607 differential genes, from which 112 significantly differential genes with p-values&lt;0.05 and |log2FC|&gt;2 were selected. Among them, 82 were up-regulated genes and 30 were down-regulated genes. Sixty-six relationships between 49 nodes were shown in the PPI network interactions graph constructed from the String database results.The results of GO analysis showed that most genes were involved in biological processes related to immune response, such as positive regulation of inflammatory response, integrated stress response signaling and toll-like receptor 4 signaling pathway. The molecular functions were mainly focused on chemokine receptor binding. the results of KEGG analysis showed that the gene products were mainly involved in cytokine-cytokine receptor interaction, IL-17 signaling pathway. The target genes screened included CXCL8 CXCL2 NFKBIZ NFKBIA IL11 IL1A,all of which have adequate immune response effects(Figure 1) Figure 1. Using the EPC algorithm in cytoHubba to screen hub genes, the graph shows the top 10 scoring genes, with different colors representing higher scores. Conclusion We have identified a series of genes associated with immunity in this study.These DEGs may provide a basis for insight into the pathogenesis of AS-associated uveitis. Further experimental studies are needed to confirm our hypothesis. References [1]Wenker K. J. &amp; Quint J. M. (2021). Ankylosing Spondylitis. In StatPearls. StatPearls Publishing *Corresponding author Jing Zhu 1 * Bo Gong 2 * 1 Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Department of Rheumatology and Immunology Chengdu China 2 Department of Health Management,Sichuan Academy of Medical Sciences&amp;Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of China Chengdu China Disclosure of Interests None declared